Objective of this project is the study of mechanism of pathogenesis of the mucopolysaccharidoses (MPS) with emphasis on brain involvement and mental retardation. We are using a comparative approach. For this purpose, the biochemical changes in glycosamingolycans (GAG), sphingolipids and pertinent lysosomal enzymes are determined in tissues from patients with various types of MPS and are compared with normal controls, and correlations are made in terms of clinical and ultrastructural findings. To complement the studies with human subjects, an animal model of mucopolysaccharidosis is being developed. The drug suramin given intravenously and intracerebrally to rats inhibits enzymes of glycosaminoglycan and sphingolipid degradation and causes accumulation of these compounds in the lysosomes, thus simulating a mucopolysaccharidosis.